Phosphorylation and destabilization of human period I clock protein by human casein kinase Iε

作者：George A. Keesler, Fernando Camacho, Yong Xia Guo, David M. Virshup, Cesare Mondadori, Zhengbin Yao · 发表于：Neuroreport · 年份：2000 · DOI：10.1097/00001756-200004070-00011 · 被引用次数：138 · 研究领域：Circadian rhythm and melatonin、Genetics, Aging, and Longevity in Model Organisms、Photoreceptor and optogenetics research

Period (PER), a central component of the circadian clock in Drosophila, undergoes daily oscillation in abundance and phosphorylation state. Here we report that human casein kinase I epsilon (hCKI epsilon) can phosphorylate human PER I (hPER I). Purified recombinant hCKI epsilon (but not a kinase negative mutant of hCKI epsilon, hCKI epsilon-K38R) phosphorylated hPER I in vitro. When co-transfected with wild-type hCKI epsilon, in 293T cells, hPER I showed a significant increase in phosphorylation as evidenced by a shift in molecular mass. Furthermore, phosphorylation of hPER I by hCKI epsilon caused a decrease in protein stability in hPER I. Whereas phosphorylated hPER I had a half-life of approximately 12 h, unphosphorylated hPER I remained stable in the cell for > 24 h. hPER I protein could also be co-immunoprecipitated with transfected hCKI epsilon as well as endogenous hCKI epsilon, indicating physical association between hPER I and hCKI epsilon proteins in vivo.